HBV感染呈世界范围内广泛流行，深入研究HBV复制的调控机制，将有助于充分了解HBV致病机理和促进抗病毒方案的发展。通过前期研究，我们发现SIRT2基因沉默可显著降低HBV DNA，HBV总RNAs和3.5-kb RNA的表达并且可明显抑制HBV启动子活性；但是，SIRT2沉默对HBV cccDNA的表达水平没有显著影响，也不能调控cccDNA微染色体组蛋白乙酰化水平。基于上述发现，本项目将在HepG2-NTCP和人原代肝细胞HBV感染模型中，系统全面分析SIRT2对HBV转录和复制的调控作用；并研究SIRT2是否通过乙酰化修饰改变HBV转录调控因子的mRNA水平和蛋白质水平，阐明SIRT2调控HBV转录和复制的分子机制；最后，在细胞模型和慢性HBV感染小鼠模型中评估SIRT2的抑制剂抗病毒效能。本项目的开展有助于完善HBV复制调控机制，也为发展新的抗病毒治疗药物奠定理论依据和实验基础。

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Therefore, characterization of HBV replication will provide valuable information for the development of anti-HBV therapeutics. From preliminary data, we found silencing of SIRT2 inhibited HBV DNA, total HBV RNAs and HBV 3.5-kb RNA levels as well as the activities of HBV promoters (HBV Cp, Xp, Sp1, Sp2). However, SIRT3 suppression did not modulate cccDNA level and deacetylate HBV cccDNA-bound H3/H4. Based on these findings, this study will further characterize the function of SIRT2 in HBV transcription and replication in HepG2-NTCP cell and human primary hepatocyte (PHH). Moreover, we will further identify whether SIRT2 could affect the mRNA level or protein level of the HBV transcription regulator through deacetylation and clarify the molecular mechanism of HBV regulation by SIRT2. Finally, we will examine the antiviral activity of SIRT2 inhibitor on HBV replication in HBV infection cell model and chronic hepatitis mouse model. This study will contribute to provide deeply understanding the mechanism of HBV replication and provide theory and experimental basis for development a novel target to treatment of hepatitis B.